title: Association of the nicotine metabolite ratio and CHRNA5/CHRNA3 polymorphisms with smoking rate among treatment-seeking smokers.
abstract: BACKGROUND
  Genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in the CHRNA5/A3/B4 gene cluster with heaviness of smoking. The nicotine metabolite ratio (NMR), a measure of the rate of nicotine metabolism, is associated with the number of cigarettes per day (CPD) and likelihood of cessation. We tested the potential interacting effects of these two risk factors on CPD.
  
  
  METHODS
  Pretreatment data from three prior clinical trials were pooled for analysis. One thousand and thirty treatment seekers of European ancestry with genotype data for the CHRNA5/A3/B4 SNPs rs578776 and rs1051730 and complete data for NMR and CPD at pretreatment were included. Data for the third SNP, rs16969968, were available for 677 individuals. Linear regression models estimated the main and interacting effects of genotype and NMR on CPD.
  
  
  RESULTS
  We confirmed independent associations between the NMR and CPD as well as between the SNPs rs16969968 and rs1051730 and CPD. We did not detect a significant interaction between NMR and any of the SNPs examined.
  
  
  CONCLUSIONS
  This study demonstrates the additive and independent association of the NMR and SNPs in the CHRNA5/A3/B4 gene cluster with smoking rate in treatment-seeking smokers.
authors.affiliation: Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Falcone
authors.forename: Christopher
authors.initials: C
authors.lastname: Jepson
authors.forename: Neal
authors.initials: N
authors.lastname: Benowitz
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.forename: Angela
authors.initials: A
authors.lastname: Pinto
authors.forename: E Paul
authors.initials: EP
authors.lastname: Wileyto
authors.forename: Don
authors.initials: D
authors.lastname: Baldwin
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
authors.forename: Riju
authors.initials: R
authors.lastname: Ray
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D002986:Clinical Trials as Topic; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009538:Nicotine / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012737:Sex Factors; D012907:Smoking / Q000235:genetics*; D016540:Smoking Cessation
chemical_list: D009419:Nerve Tissue Proteins; D009538:Nicotine; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human